Hematoporphyrin Oligomer Research Articles

In vivo transport and pharmacokinetic behavior of tumour photosensitizers.

The mechanisms by which photodynamic sensitizers are transported in the bloodstream influence their distribution among normal and tumour tissues, as well as their partitioning among the various compartments of tumour tissues. Column chromatographic analysis and density gradient ultracentrifugation of sera obtained from both patients and experimental animals show that hydrophilic photosensitizers (e.g. haematoporphyrin, and tetrasulphonated porphyrins and phthalocyanines) are largely transported by albumin and globulins and mainly deposited in the vascular stroma of tumours. More hydrophobic photosensitizers (haematoporphyrin oligomers, porphyrin esters, monosulphonated or unsubstituted phthalocyanines) are preferentially incorporated in the lipid core of lipoproteins. Tightly aggregated dyes partly circulate as unbound pseudomicellar structures which can be entrapped in the interstitial regions of the tumour, localize in macrophages, or enter neoplastic cells via pinocytotic processes. Low density lipoproteins (LDL), which are endocytosed by neoplastic cells through a specific receptor-mediated pathway, display the most selective release of photosensitizers to tumours. The binding of the injected photosensitizer to LDL can be enhanced by preincorporation of the dye in liposomal vesicles which are in a quasi-solid state at the body temperature.

Photodynamic Therapy for Squamous Cell Carcinoma Invading Alveolar Bone in a Mouse Model

Objective: To examine the effects of photodynamic therapy on squamous cell carcinoma invading the alveolar bone.Materials and Methods: NR-S1 tumour was transplanted into an upper incisor extraction socket of 5-week-old male C3H/HeNCrj mice. Twenty six mice were divided into 4 groups: 8 received no treatment, 5 received a photosensitiser (haematoporphyrin oligomers), 5 underwent neodymium:YAG laser irradiation, and 8 received a photosensitiser followed by laser irradiation. The area of tumour necrosis was measured by image analysis of haematoxylin and eosin-stained specimens. Proliferative activity of cells in the tumour and normal tissue was evaluated by immunohistochemistry.Results: The patterns of tumour growth and spread were similar in the control, photosensitiser, and laser groups. Although photosensitiser followed by laser irradiation induced tumour necrosis at a higher rate than the other 3 treatments, surviving tumour cells were found at the tumour margin and in the extraction socket.Conclusion: Photosensitiser followed by laser irradiation is not an effective treatment for squamous cell carcinoma involving alveolar bone.

Hyperthermic photodynamic therapy combined with topical administration of OK-432 in the mouse carcinoma

This study investigated the combined effect of photodynamic therapy (PDT) using high power laser irradiation (HPL), which generates both a hyperthermic and a photodynamic effect, and OK-432 on NR-S1 mouse squamous cell carcinoma. The photosensitizer (haematoporphyrin oligomers 20 mg/kg BW) was injected to the mice intraperitoneally 48 h before laser irradiation. OK-432 was injected into the tumour 3 h prior to laser irradiation. The experimental protocols consisted of HPL–PDT with or without OK-432, low power laser PDT with or without OK-432, HPL alone and OK-432 alone, and a control group. The tumour necrotic area was determined, and tumour sizes were measured 3, 7 and 10 days after each protocol. The anti-tumour effect of HPL–PDT was enhanced by preadministration with OK-432. Treatment with OK-432 alone or hyperthermic HPL irradiation presented little anti-tumour effect. HPL–PDT in combination with OK-432 topically administered 3 h before photo-irradiation is considered to be a promising therapeutic modality.

Cell kinetics of mouse tumour subjected to photodynamic therapy--evaluation by proliferating cell nuclear antigen immunohistochemistry.

Tumour reaction and tumour cell kinetics in mouse NR-S1 carcinoma subjected to photodynamic therapy (PDT) were evaluated by percentage of necrotic area as well as by proliferating cell nuclear antigen (PCNA) immunohistochemistry, and an effective PDT fractionation interval was proposed. PDT was carried out in mouse NR-S1 carcinomas using a photosensitizer (haematoporphyrin oligomers: 20 mg kg body weight) and pulsed Nd:YAG dye laser. The percentages of tumour necrotic area and PCNA labelling indices (LIs) in the tumours were assessed at intervals of 0, 0.5, 5, 2.5, 6, 24, 48, and 72 h after PDT. It was demonstrated that maximum damage and repopulation of the tumour cells emerge at 24 and 48 h, respectively, following PDT, suggesting that subsequent light treatment should be performed within 24 h to enhance the therapeutic effect of PDT.

Tumour destruction and proliferation kinetics following periodic, low power light, haematoporphyrin oligomers mediated photodynamic therapy in the mouse tongue.

Photodynamic therapy (PDT) is an experimental modality in the treatment of cancer. It involves photochemical reactions that require the interaction of a photosensitising drug, light and oxygen. The development of an efficient protocol based on assuring oxygen availability through modulation of the incident light power density and its mode of delivery was addressed in this study. An estimated energy dose of 180 J/cm2 of 630 nm light from pulsed Nd:YAG dye laser was delivered 24 h after injection of 10 mg/kg haematoporphyrin oligomers in C3H/HeNCrj mice bearing the transplantable squamous cell carcinoma NR-S1, by either of these light regimens: (1) 5 mJ/cm2/pulse for 30 min, 1 h dark interval, followed by another 30 min exposure to the same power (low power, periodic light regimen) or (2) 15 mJ/cm2/pulse for 20 min (high power, continuous light regimen). Results showed a higher mean percentage area of tumour destruction with the low power, periodic light regimen at 54.34% in contrast to 12.44% of the high power, continuous light regimen 2 days after PDT. Furthermore, the mean bromodeoxyuridine labelling indices of the remaining viable-appearing cancer cells were 27.90 and 42.41, respectively, indicating a smaller tumour growth fraction with the former regimen. These results suggest that use of low power, periodically delivered light increases the antitumour efficacy of PDT.

ヒト悪性黒色腫由来培養細胞浮遊液系での光増感反応による活性酸素の動態

We investigated the sensitizing efficacy (yield of active oxygen production) of pheophorbide derivative (PH-1126), phthalocyanine derivatives (Al-Pc) and hematoporphyrin oligomer (HpO) by spin trapping method of electron spin resonance in cethyltrithylammonium bromide (CTAB) solution or human malignant melanoma floating cells (HMF). In the results, (1) Type I reaction was predominant in 0.1mM-CTAB solution. (2) In 10mM-CTAB solution, Type I and Type II reactions included. (3) Type II reaction was predominant in HMF cell suspension. It was suggested that the formation of the sensitizers incorporated in HMF cells must be monomer form.

Combination Effect of Hyperthermia and Photodynamic Therapy on Carcinoma

We investigated the time course of hematoporphyrin oligomer uptake in squamous cell carcinoma transplanted into C3H mice after intraperitoneal injection by measuring its fluorescence intensity. The intensity peaked 83 hours after the injection. The tumors disappeared after an average of 4.12 days with a single application of photodynamic therapy or microwave hyperthermia 83 hours after hematoporphyrin oligomer injection. However, all the tumors treated with these single modalities regrew within 4 weeks after the treatments. Therefore, we investigated the therapeutic effect of microwave hyperthermia in combination with photodynamic therapy. As a result, the combination effect was strongest when high-dose therapy was used as the first choice, irrespective of the order of the treatments, and no tumor regrowth occurred for 45 days.

A sensitizing effects of hematoporphyrin oligomer and caffeine for the DNA damade irradiated by X-ray on experimental skin tumors

A sensitizing effects of hematoporphyrin oligomer and caffeine for the DNA damade irradiated by X-ray on experimental skin tumors

Combination effect of photodynamic therapy and microwave hyperthermia on experimental squamous cell carcinoma in vivo

We investigated the time course of Hematoporphyrin oligomer (HpO) uptake to squamous cell carcinoma (SCC) transplanted into C3H mice after intraperitoneal (i.p.)-injection by measuring its fluorescence intensity. The fluorescence intensity was maximum at 83 hr after the i.p.-injection. The tumors once disappeared by the single application of photodynamic therapy (PDT) or microwave hyperthermia at 83 hr after HpO i.p.-injection. However, all the tumors treated with these single modalities recurred within 4 weeks after the treatments. Therefore, we investigated the therapeutic effect of microwave hyperthermia in combination with PDT at 83 hr after HpO i.p.-injection. As the results, the combination effect was the strongest when high-dose therapy was used as the first choice of therapy, irrespective of the orders of the treatments and no tumor regrowth occurred over 45 days after tumor disappearance.

実験移植扁平上皮癌におけるヘマトポルフィリンオリゴマーの取込みと光力学的治療及びマイクロ波温熱治療効果

実験移植扁平上皮癌におけるヘマトポルフィリンオリゴマーの取込みと光力学的治療及びマイクロ波温熱治療効果

Spectroscopic study of haematoporphyrin oligomers in tumour tissue

Fluorescence spectra of modified haematoporphyrin (Hp) oligomers (of mean molecular weights 3000, 5000 and 12000) and Photofrin II in tumour tissue were semi-quantitatively measured by a reflection method. Characteristic peaks of the emission spectra, obtained by excitation at 370 nm, appeared at 677 nm and also at 634 and 695 nm. The intensity ratio of the emission band (677 nm) to the other emission bands (633 nm) increased in accordance with increases in the oligomer molecular weight. The integral intensity of the fluorescence emission spectra of oligomer 3000 (i.e., the pentamer of Hp in tumour tissue) was about two times greater than that of Photofrin II.